Artificial biomaterials are introduced within the human body for repairing damages therein. The body conditions, however, are a severe environment and the combination of constant exposure to moisture, salt, biofluids, and continuous use over potentially decades provides a challenging environment. The body is also sensitive to foreign materials and may shows signs of poisoning, rejection and allergic responses.
All materials implanted within the body elicit a response from the surrounding tissue. “Bioactivity” is a unique property associated with the ability of materials that are foreign to the body to integrate and form a strong bond with living tissue. The interfacial bond may prevent rejection, accelerate the healing process, and increase the strength and durability of implants, devices, and/or repairs.
Bioactive materials include bioactive glasses, glass ceramics and ceramics. Bioactive ceramics are, for example, calcium phosphates and aluminum calcium phosphates and are used in orthopedic surgery. The most common problems with these materials relate to crystallization. The crystalline structure makes them difficult to work with and it is difficult to control the crystallization. The wear and degradation mechanisms, as well as durability of the ceramics, are not well understood. Bioactive glass ceramics are glassy materials having crystalline particles embedded in the amorphous glass phase. Ceravital is a glass ceramic that contains a glassy phase and an apatite crystalline phase.
Bioactive glasses, marketed as BIOGLASS, are amorphous materials. These materials encourage the growth of living bone onto their surfaces by slowly releasing calcium (Ca2+) and phosphate ions (PO43−) that are an essential part of the bodies bone building mechanism. Bioactive glasses have been in use for about 20 years as bone filling materials and prostheses in odontology, orthopedics and ophthalmology and some of the existing bioactive glasses can bond to both soft and hard tissue.
Three key compositional features distinguish bioactive glasses from traditional soda-lime-silica glasses. Conventional bioactive glasses typically contain less than 60 mole percent SiO2, high Na2O and CaO content (20-25% each), and a high molar ratio of calcium to phosphorus (ranging around five). Currently, bioactive powders are produced by conventional processing techniques well known in the art. The various constituents (for example, Na2CO3, CaCO3, P2O5 and SiO2) are usually mixed in a suitable mixing device, such as a rolling mill, and then heated in a platinum crucible to a temperature (generally between 1250 and 1400° C.) sufficient to cause the particles to melt and coalesce. The use of such high temperatures and specialized equipment results in significant production costs.
As pointed out by Hench et al. U.S. Pat. No. 5,074,916, conventional bioactive glasses suffer from other shortcomings. These compositions tend to require an alkali metal oxide such as Na2O to serve as a flux or aid in melting or homogenization. However, the presence of alkali metal oxide ions results in a high pH at the interface between the glass and surrounding fluid or tissue; in the body, this can induce inflammation. Furthermore, the rate of tissue repair, which drives the interfacial tissue-glass bonding promoted by the bioactive material, tends to vary within a narrow pH range. Conventional bioactive glasses also tend to be difficult to mix to homogeneity, a criterion that holds great importance for quality control of materials intended for implantation in the body. This is due to the relatively large grain size of the glass precursors, which generally measure approximately 10 to 1000 microns in diameter. It is difficult to obtain “molecular scale” mixing, i.e., homogeneity at the molecular level, using ordinary mixing techniques, such as stirring of the viscous glass melts.
Known bioactive glasses have attained clinical use as bone filling materials. They tend, however, to devitrify (crystallize) and their working range is narrow. Although the glasses are vitreous materials, some of them crystallize at low temperatures (about 600° C.). This makes them difficult to sinter into a product or to use for the manufacturing of spherical granules. They are often also phase separated due to their low content of silica, and the glass composition is therefore different from batch to batch.
The use of bioactive glasses is further restricted in applications where they are mixed as powders with biocompatible polymers to form a composite. The powders have a brittle or shard-like character and thus form an extremely abrasive surface that may cause irritation or excessive wear.
U.S. Pat. No. 5,508,342 to Antonucci et al. discloses a mineralizing agent for skeletal tissue comprising a mixture of an unsaturated monomer system, and a particulate mineralizing agent comprising amorphous calcium phosphate. However, amorphous calcium phosphates are brittle and have very poor strength and therefore are unsuitable in applications that require high-hardness, strength and toughness.
U.S. Pat. No. 5,952,399 to Rentsch, discloses a dental material based on an organic polymerizable binding agent, a polymerization catalyst, and relative to the dental material, 1-95 weight percent of an inorganic filler having a refractive index less than 1.58, wherein the filler comprises mixed-apatites, such as fluoroapatites, apatites containing sulfates and variations thereof. Rentsch contemplates significant chemical substitution of the hydroxyapatite lattice to adjust the refractive index from 1.63 to the preferred range near 1.52-1.56. Rentsch discloses compositions within or near this range, for example, Ca4Na6(SO4)F2; η=1.52, and Ca8Na2[(PO4)4(SO4)2]F2; η=1.57. However, the disclosed materials have chemical compositions that are very different from hydroxyapatite and it is not clear if such materials are bioactive and may exchange Ca2+ and (PO4)3− ions with a biological environment. Further, fluoroapatites are very insoluble, have poor hardness and are brittle and therefore are unsuitable in applications that require high-hardness, strength and toughness.
WO 2006/055317A1 patent application to Rusin et al. discloses dental compositions and methods of making and using dental compositions that include a calcium and phosphorous releasing glass. However, as described above, bioactive glasses are difficult and expensive to prepare and have poor mechanical and abrasion wear properties.
U.S. Pat. No. 7,090,720 to Kessler et al. discloses a dental filling material for an aesthetic permanent dental filling, the dental filling material containing a resin matrix and up to 87 percent by weight of glass particles, wherein the glass particles have an average particle size less than 50 microns, the glass particles comprise bioactive glass particles and non-bioactive dental glass particles, the bioactive glass particles are capable of forming a hydroxyl apatite layer and comprise a bioactive glass material in which calcium is replaced in part with strontium and/or barium. Further, the resin matrix has an index of refraction approximately equal to an index of refraction of the bioactive glass particles and/or an index of refraction of the non-bioactive dental glass particles. However, as described above, bioactive glasses are difficult and expensive to prepare and have poor mechanical and abrasion wear properties.
U.S. Pat. No. 5,074,916 to Hench et al. discloses a bioactive composition prepared using a sol-gel process, and consisting essentially of more than 60 but no more than 86 weight percent SiO2, at least 4 but less than 33 weight percent CaO and at least 3 but no more than 15 weight percent P2O5. The sol-gel process may form glasses at processing temperatures below the melt temperature of the glass. However, the process uses flammable hydrocarbon solvents, has a very low process yield and produces glasses with extremely high surface areas from about 200-500 m2/g. The high surface area is problematic since it makes the materials very difficult to homogeneously disperse into polymers or monomers for the preparation of composites.